APTO-253 Is a New Addition to the Repertoire of Drugs that Can Exploit DNA BRCA1/2 Deficiency.

ABSTRACT: APTO-253 is a small molecule with antiproliferative activity against cell lines derived from a wide range of human malignancies. We sought to determine the mechanisms of action and basis for resistance to APTO-253 so as to identify synthetic lethal interactions that can guide combination studies. The cellular pharmacology of APTO-253 was analyzed in Raji lymphoma cells and a subline selected for resistance (Raji/253R). Using LC/MS/ESI analysis, APTO-253 was found to convert intracellularly to a complex containing one molecule of iron and three molecules of APTO-253 [Fe(253)₃]. The intracellular content of Fe(253)₃ exceeded that of the native drug by approximately 18-fold, and Fe(253)₃ appears to be the most active form. Treatment of cells with APTO-253 caus

SUBMITTER: Tsai CY 

PROVIDER: S-EPMC7087411 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature